Lipid Nanodiscs Unlock the Potential of Cytokine Treatment
Researchers at the University of Texas at Austin created a nanocarrier for stem cell factor, a regenerative cytokine. The nanotechnological approach renders the treatment much safer, as previous attempts to use stem cell factor as a pro-angiogenic treatment have been hampered by severe allergic reactions in some recipients. This latest technology helps to unlock the potential of the regenerative treatment. The researchers used a transmembrane form of the protein treatment, which is typically anchored to a cell membrane, and delivered it using lipid nanodiscs. The treatment does not appear to activate the immune system in a harmful way, and so should be much safer.
Regenerative medicine holds enormous potential in treating patients who have suffered tissue damage after a cardiovascular event. Cytokines that can stimulate new blood vessels to grow could help to repair tissues that are damaged after a stroke or heart attack, for instance. However, just like any small molecule drug, biological treatments can have negative effects if used inappropriately, and the devil is in the details.
In this instance, these researchers turned to a cytokine that had previously been written off as dangerous. The cytokine is called stem cell factor, and it stimulates stem cells to grow. It can help to regenerate blood vessels and restore blood flow to ischemic tissues, making it a prime candidate for a pro-angiogenic regenerative therapeutic. However, when tested in a clinical trial as a treatment post-stroke, it had the unfortunate side-effect of stimulating mast cells to grow. These white blood cells are involved in allergic reactions, and in this case several patients had serious allergic reactions following treatment.
However, for these researchers, hope was not lost. They turned to another form of stem cell factor, which is usually anchored to cell membranes rather than floating around in the blood. “We found this transmembrane stem cell factor has all the necessary therapeutic properties and without activating the immune system and causing allergic reaction,” said Eri Takematsu, a researcher involved in the study.
To stop the cytokine from clumping together and to help deliver it intact to the areas it needs to go in the body, the researchers encapsulated it in lipid nanodiscs. “This type of nanodisc is something people haven’t explored very much developing therapeutics before,” said Aaron Baker, another researcher involved in the study. “It makes a little island of lipid around the transmembrane stem cell factor and holds it together with a ring of proteins, kind of like a lariat.”
So far, the researchers have tested the treatment in mice, and showed that it could help to regenerate blood vessels without causing allergic reactions.
Study in Nature Communications: Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation
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